Therapeutic potential of beta-caryophyllene against aflatoxin B1-Induced liver toxicity: biochemical and molecular insights in rats

• Published in: Chemico-biological interactions Vol. 348; p. 109635
• Main Authors: Da Silveira, Alice Rosa, Rosa, Érica Vanessa Furlan, Sari, Marcel Henrique Marcondes, Sampaio, Tuane Bazanella, Dos Santos, Jamila Trindade, Jardim, Natália Silva, Müller, Sabrina Grendene, Oliveira, Mauro Schneider, Nogueira, Cristina Wayne, Furian, Ana Flávia
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-10-2021
• Subjects: Aflatoxin B1 - toxicity; Animals; Antioxidants - pharmacology; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - prevention & control; Hepatorenal toxicity; Interleukin-1beta - metabolism; Keap1/Nrf2; Kelch-Like ECH-Associated Protein 1 - metabolism; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Mycotoxins; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Oxidative Stress - drug effects; Polycyclic Sesquiterpenes - chemistry; Polycyclic Sesquiterpenes - pharmacology; Rats; Rats, Wistar; Rodents; Sesquiterpenes - pharmacology; Oxidative stress; Hepatorenal toxicity; Rodents; Mycotoxins; Keap1/Nrf2
• ISSN: 0009-2797; 1872-7786; 1872-7786
• DOI: 10.1016/j.cbi.2021.109635

Aflatoxin B1 (AFB1) is a mycotoxin highly toxic and carcinogenic to humans due to its potential to induce oxidative stress. The Beta-caryophyllene (BCP) have been highlighted for its broad spectrum of pharmacological effects. The present study aimed to investigate the beneficial effects of BCP against the susceptibility of hepatic and renal tissues to AFB1 toxicity, in biochemical parameters to assess organ function, tissue oxidation, and the immunocontent of oxidative and inflammatory proteins. Male Wistar rats was exposed to AFB1 (250 μg/kg, i.g.) and/or BCP (100 mg/kg, i.p.) for 14 successive days. It was found that exposure to AFB1 did not change the measured renal toxicity parameters. Also, AFB1 increased liver injury biomarkers (gamma glutamyl transferase and alkaline phosphatase) and reduced levels of non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol), however did not cause changes in the lipid peroxidation levels. Moreover, AFB1 interfered in oxidative pathway regulated by Kelch-like ECH-associated protein (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2), overacting Glutathione-S-Transferase (GST) activity. Lastly, a main effect of AFB1 on the total interleukin 1 beta (IL-1β) was observed. Remarkably, the associated treatment of AFB1 + BCP improved altered liver parameters. In addition, BCP and AFB1 + BCP groups showed an increase in the levels of inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ). Thus, these results indicated that BCP has potential protective effect against AFB1 induced hepatotoxicity.
•AFB1 exposure causes selective liver toxicity.•Antioxidant system alterations seems to be associated with AFB1 hepatotoxicity.•BCP restores AFB1-induced changes in the liver.•BCP upregulating the Nrf2 pathway on the liver.